Evidence for striatal dopamine release during a video game

Dopaminergic neurotransmission may be involved in learning, reinforcement of behaviour, attention, and sensorimotor integration,. Binding of the radioligand 11C-labelled raclopride to dopamine D2 receptors is sensitive to levels of endogenous dopamine, which can be released by pharmacological challenge. Here we use 11C-labelled raclopride and positron emission tomography scans to provide evidence that endogenous dopamine is released in the human striatum during a goal-directed motor task, namely a video game. Binding of raclopride to dopamine receptors in the striatum was significantly reduced during the video game compared with baseline levels of binding, consistent with increased release and binding of dopamine to its receptors. The reduction in binding of raclopride in the striatum positively correlated with the performance level during the task and was greatest in the ventral striatum. These results show, to our knowledge for the first time, behavioural conditions under which dopamine is released in humans, and illustrate the ability of positron emission tomography to detect neurotransmitter fluxes in vivo during manipulations of behaviour.

[1]  J. Glowinski,et al.  Selective activation of the mesocortical DA system by stress , 1976, Nature.

[2]  G. Arbuthnott.  The dopamine synapse and the notion of ‘pleasure centres’ in the brain , 1980, Trends in Neurosciences.

[3]  R. Wise.  The dopamine synapse and the notion of ‘pleasure centers’ in the brain , 1980, Trends in Neurosciences.

[4]  T. Robbins,et al.  Functions of dopamine in the dorsal and ventral striatum , 1992 .

[5]  W. Schultz,et al.  Responses of monkey dopamine neurons during learning of behavioral reactions. , 1992, Journal of neurophysiology.

[6]  G. Sedvall,et al.  Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. , 1992, Archives of general psychiatry.

[7]  R. Myers,et al.  Quantitation of Carbon‐11‐labeled raclopride in rat striatum using positron emission tomography , 1992, Synapse.

[8]  J S Fowler,et al.  Reproducibility of repeated measures of carbon-11-raclopride binding in the human brain. , 1993, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[9]  W. Schultz,et al.  Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  J S Fowler,et al.  Effects of central cholinergic blockade on striatal dopamine release measured with positron emission tomography in normal human subjects. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Jean Logan,et al.  Imaging endogenous dopamine competition with [11C]raclopride in the human brain , 1994, Synapse.

[12]  J. Salamone,et al.  Nucleus accumbens dopamine release increases during instrumental lever pressing for food but not free food consumption , 1994, Pharmacology Biochemistry and Behavior.

[13]  A M Graybiel,et al.  The basal ganglia and adaptive motor control. , 1994, Science.

[14]  M. Nomura,et al.  The relationship between learning performance and dopamine in the prefrontal cortex of the rat , 1994, Neuroscience Letters.

[15]  N. Volkow,et al.  Effects of Blood Flow on [11C]Raclopride Binding in the Brain: Model Simulations and Kinetic Analysis of PET Data , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[16]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[17]  Evan D. Morris,et al.  In vivo imaging of neuromodulation using positron emission tomography: Optimal ligand characteristics and task length for detection of activation , 1995 .

[18]  D. Brooks.  The role of the basal ganglia in motor control: contributions from PET , 1995, Journal of the Neurological Sciences.

[19]  N. Alpert,et al.  In vivo imaging of neuromodulatory synaptic transmission using PET: A review of relevant neurophysiology , 1995 .

[20]  Christopher J. Taylor,et al.  A cluster analysis approach for the characterization of dynamic PET data , 1996 .

[21]  A. Lammertsma,et al.  Simplified Reference Tissue Model for PET Receptor Studies , 1996, NeuroImage.

[22]  R. Myers.  Quantification of brain function using PET , 1996 .

[23]  A. Gratton,et al.  Behavior-Relevant Changes in Nucleus Accumbens Dopamine Transmission Elicited by Food Reinforcement: An Electrochemical Study in Rat , 1996, The Journal of Neuroscience.

[24]  Vincent J. Cunningham,et al.  Parametric Imaging of Ligand-Receptor Binding in PET Using a Simplified Reference Region Model , 1997, NeuroImage.

[25]  W. Schultz.  Dopamine neurons and their role in reward mechanisms , 1997, Current Opinion in Neurobiology.

[26]  W C Eckelman,et al.  Kinetic Modeling of [11C]Raclopride: Combined PET-Microdialysis Studies , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[27]  A. Malhotra,et al.  Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[28]  P B Hoffer,et al.  Microdialysis and SPECT measurements of amphetamine‐induced dopamine release in nonhuman primates , 1997, Synapse.

[29]  J S Fowler,et al.  Reproducibility of repeated measures of endogenous dopamine competition with [11C]raclopride in the human brain in response to methylphenidate. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.